GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis
Open accessAbstract
Aims/hypothesis GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results.Methods In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine).Results We estimate that there is a 98% probability that 20 μg GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients.Conclusions/interpretation The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.
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Trials of antigen therapy with different GAD protein forms have had mixed results, mostly negative.
“Antigen-based trials have used various forms of glutamate decarboxylase (GAD) protein, which have shown mixed but mostly negative results.139–141”
From Type 1 diabetes (2018) · cites this paper as [139]
The Introduction reports mixed trial findings: two studies had non-significant primary endpoints, while the third had a non-significant primary endpoint but significant secondary results. That supports the characterization of trial results as mixed and mostly negative on primary endpoints. However, the Methods say the trials used the same study drug with different dosing regimens, not different GAD protein forms; the Discussion also concludes that a small positive biological effect is highly likely. (LLM, conf=0.86)
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- Authors
- the Type 1 Diabetes TrialNet Study Group, Beam, C. A., MacCallum, C., Herold, K. C., Wherrett, D. K., Palmer, J., & Ludvigsson, J.
- Affiliations
- Western Michigan University (US)
- University of Toronto (CA)
- Linköping University (SE)
- Corresponding author
- Beam, Craig A.
- Venue
- Diabetologia
- Published
- 2016-10-04
- Volume
- 60
- Issue
- 1
- Pages
- 43-49
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC5856235
- OpenAlex
- W2528836831
- Cited by
- 53
- References
- 20
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 11 · 2021: 5 · 2020: 12 · 2019: 1 · 2018: 6 · 2017: 3
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Juvenile Diabetes Research Foundation (1-INO-20140170-A-V)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes, alum adjuvant, newly diagnosed diabetes, immunotherapy
- MeSH terms
- Adolescent, Adult, Bayes Theorem, Child, Diabetes Mellitus, Type 1, Female, Glutamate Decarboxylase, Humans, Insulin, Male, Middle Aged, Vaccines, Young Adult
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